Estudo das propriedades citotóxica da nor-β-lapachona e seu derivado nitrofenilamino em células HL-60

Abstract

The quinone moiety has been identified as an important pharmacophoric group for cytotoxic activity of several compounds clinically used, constituting just one of the major classes of anticancer agents. β-lapachone is one of the most studied quinones in the last years. Its most important applications are related to its action against several cancer cells. Its derivative, nor-β-lapachone (compound 1), has similar anticancer activity. Thus, the aim of this work was to evaluate the mechanism of action involved in nor--lapachone and its nitrophenylamino derivative (compound 2) cytotoxicity in a leukemia cells model of HL-60 cell line. Initially it was investigated the effect of both the compounds on HL-60 cells viability after 24 hours of incubation, showing IC50 values of 2.92 and 0.48 μM to compounds 1 and 2, respectively. Considering the selectivity, compound 1 showed strong selectivity to cancer cells, while its derivative was only partially selective. Studies performed in HL-60 cells, after 24 hours, indicated that compound 2 induces cell death by apoptosis as showed by morphological changes, DNA fragmentation, mitochondrial membrane depolarization and phosphatidylserine externalization. Both tested compounds increased generation of reactive oxygen species (ROS). Our results suggest that a nitrophenylamino radical introduction at position 3 of the furane ring enhances the cytotoxicity of nor--lapachone in HL-60 cell line. These findings highlight the potential of these synthetic quinones as prototypes molecules to produce new compounds with anticancer properties.